4-BROMOPYRIDIN-2-OL

Y. l-Methyl-S-^λ.S.S-tetramethyl-lJ^-dioxaborolan^-vnpyridin^qHl-one; Step a: 4-Bromopyridin-2(lH)-one; To a solution of 4-bromo-2-methoxypyridine (1.0 g, 5.3 mmol) in 1, 4-dioxane(26 mL) was added 4M HCl aqueous solution (13 mL). The reaction was heated at 90 In a dry Schlenk tube 4-bromo-2-chloropyridine (3.71 g, 19.3 mmol) was dissolved in 50 mL of t-AmylOH and KOt-Bu (10.8 g, 96.5 mmol) was added. The mixture was stirred at 80 °C for 16 h. The solvent was removed under reduced pressure and the residue was dissolved in 20 mL of HCOGeneral procedure: To 4b/c/d (prepared above) and sodium acetate (2.0 eq.) in acetic acid (1.0M)was heated at 150°C in a sealed tube for 72h. The mixture was cooled to r.t. andconcentrated under reduced pressure. The residue was partitioned between ethylacetate (3 mL/mmol) and cold water (3mL/mmol). The aqueous layer was extractedwith ethyl acetate (3mL/mmol; 4x). The combined organic layers were successivelywashed with sat. NaHCO3 (1 mL/mmol), brine, dried (Na2SO4), filtered andconcentrated under reduced pressure. The crude material was purified by flashchromatography on silica gel to give products 1b/c/d, and details of individualcompounds are provided below.To a solution of 2-benzyloxy-4-bromopyridine 6 (201 mg, 0.8 mmol) in MeOH(4.5 mL) was added conc. HCl (2.3 mL). The mixture was heated at reflux overnight.Then the reaction mixture was cooled to room temperature and concentrated underreduced pressure. The residue was poured into cold water and carefully quenchedwith aq. sat. Na2CO3. The aqueous layer was extracted with ethyl acetate (3x). Thecombined organic layers were washed with brine, dried (Na2SO4), filtered andconcentrated under reduced pressure. The crude was purified by flash chromatography on silica gel (EtOAc/MeOH: 98/2) to give 1c (109 mg, 82percent) as acolorless solid. Data for 1c are reported above.[01068] Sodium hydride (111 mg, 4.62 mmol, 60% in mineral oil) was added to a stirred solution of 4-bromopyridin-2(lH)-one (400 mg, 2.31 mmol) in 15 mL of THF at 0C. After stirring for 20 min at 0C, bromofluoromethane (517 mg, 4.62 mmol) was added. The mixture was then stirred at 50C for 1 h, quenched with H20 and extracted with EtOAc (30 mL X 3). The combined organic phases were washed with brine, dried over anhydrous Na2S04, concentrated under reduced pressure and purified by silica gel column (50% EtO Ac/petroleum ether) which gave 400 mg of 4-bromo-l-(fluoromethyl)pyridin-2(lH)-one as white solid (84% yield). LCMS: mh 207.9 [M+H]+; = 1.46 min.Potassium carbonate (477 mg, 3.45 mmol) was added to a suspension of A mixture of To an ice-cold solution of 2-hydroxy-4-bromopyridine (5.75 mmol) in THF was added NaH (5.75 mmol) portion-wise. The reaction mixture was stirred in an ice-bath for 15 min followed by addition of halide or iodine (17.24 mmol). The resulting reaction mixturewas stirred at room temperature for 16 h. After the completion of the reaction, 20 mL of H2O was added and the reaction mixture was extracted with EtOAc 3 times. The combined organic layer was collected and rinsed with brine. The mixture was evaporated to obtain the crude product and purified by silica gel for 3a-3d. 4.1.2.1. 4-bromo-1-methylpyridin-2(1H)-one (3a): [40]. Yellow solid. Yield: 87%. HRMS (ESI) m/z calcd for C6H7BrNO [M+H]+:187.9706, found: 187.9702.General procedure: To an ice-cold solution of 2-hydroxy-4-bromopyridine (5.75 mmol) in THF was added NaH (5.75 mmol) portion-wise. The reaction mixture was stirred in an ice-bath for 15 min followed by addition of halide or iodine (17.24 mmol). The resulting reaction mixturewas stirred at room temperature for 16 h. After the completion of the reaction, 20 mL of H2O was added and the reaction mixture was extracted with EtOAc 3 times. The combined organic layer was collected and rinsed with brine. The mixture was evaporated to obtain the crude product and purified by silica gel for 3a-3d.General procedure: To an ice-cold solution of 2-hydroxy-4-bromopyridine (5.75 mmol) in THF was added NaH (5.75 mmol) portion-wise. The reaction mixture was stirred in an ice-bath for 15 min followed by addition of halide or iodine (17.24 mmol). The resulting reaction mixturewas stirred at room temperature for 16 h. After the completion of the reaction, 20 mL of H2O was added and the reaction mixture was extracted with EtOAc 3 times. The combined organic layer was collected and rinsed with brine. The mixture was evaporated to obtain the crude product and purified by silica gel for 3a-3d.General procedure: To an ice-cold solution of 2-hydroxy-4-bromopyridine (5.75 mmol) in THF was added NaH (5.75 mmol) portion-wise. The reaction mixture was stirred in an ice-bath for 15 min followed by addition of halide or iodine (17.24 mmol). The resulting reaction mixturewas stirred at room temperature for 16 h. After the completion of the reaction, 20 mL of H2O was added and the reaction mixture was extracted with EtOAc 3 times. The combined organic layer was collected and rinsed with brine. The mixture was evaporated to obtain the crude product and purified by silica gel for 3a-3d.

Molecular Weight:174.00
XLogP3:0.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:172.94763
Monoisotopic Mass:172.94763
Topological Polar Surface Area:29.1
Heavy Atom Count:8
Complexity:171
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes